Radiation environment and shielding for early manned Mars missions

The problem of shielding a crew during early manned Mars missions is discussed. Requirements for shielding are presented in the context of current astronaut exposure limits, natural ionizing radiation sources, and shielding inherent in a particular Mars vehicle configuration. An estimated range for shielding weight is presented based on the worst solar flare dose, mission duration, and inherent vehicle shielding

2008 Survey of the Performance of American Elections: Final Report

Analyzes results of a survey on the 2008 elections voting experience, voter confidence in the system, reasons for not voting, and support for reform proposals. Examines how age, race/ethnicity, and length of residency affect voters' experiences

No-till Forage Establishment in Alaska

We assessed the effectiveness of no-till forage establishment at six Alaska locations: Anchor Point, Sterling, Point MacKenzie, Palmer, Delta Junction, and Fairbanks. Directly seeding grass into established grass stands generally did not improve forage yields or quality. Seeding rate had little effect on establishment of newly seeded forages in no-till. Grass yields were depressed when companion crop yields were high, and they typically did not recover in subsequent years. Red clover established well, producing high yields of good quality forage under no-till at Point MacKenzie, but established poorly at Anchor Point and Delta Junction. These results indicated that no-till seeding of most forage crops into declining grass stands is not likely to be successful in Alaska with current available technology

Biological characteristics and mortality of western butterfish (Pentapodus vitta), an abundant bycatch species of prawn trawling and recreational fishing in a large subtropical embayment

The western butterfish (Pentapodus vitta) is numerous in the bycatch of prawn trawling and recreational fishing in Shark Bay, Western Australia. We have thus determined crucial aspects of its biological characteristics and the potential impact of fishing on its abundance within this large subtropical marine embayment. Although both sexes attained a maximum age of 8 years, males grow more rapidly and to a larger size. Maturity is attained at the end of the first year of life and spawning occurs between October and January. The use of a Bayesian approach to combine independent estimates for total mortality, Z, and natural mortality, M, yielded slightly higher point estimates for Z than M. This result indicates that P. vitta is lightly impacted by fishing. It is relevant that, potentially, the individuals can spawn twice before recruitment into the fishery and that 73% of recreationally caught individuals are returned live to the water

Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin”

A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted

What makes stroke rehabilitation patients complex? Clinician perspectives and the role of discharge pressure

Background: Approximately 80% of people who survive a stroke have on average five other conditions and a wide range of psychosocial issues. Attention to biopsychosocial issues has led to the identification of ‘complex patients’. No single definition of ‘patient complexity’ exists, therefore applied health researchers seek to understand ‘patient complexity’ as it relates to a specific clinical context. Objective: To understand how ‘patient complexity’ is conceptualized by clinicians, and to position the findings within the existing literature on patient complexity. Methods: A qualitative descriptive approach was utilized. Twenty-three rehabilitation clinicians participated in four focus groups. Results: Five elements of patient complexity were identified: medical/functional issues, social determinant factors, social/family support, personal characteristics, and health system factors. Using biopsychosocial factors to identify complexity results in all patients being complex; operationalization of the definition led to the identification of systemic elements. A disconnect between acute, inpatient rehabilitation and community services was identified as a trigger for increased complexity.Conclusions: Patient complexity is not a dichotomous state. If applying existing complexity definitions, all patients are complex. This study extends the understanding by suggesting a structural element of complexity from manageable to less manageable complexity based on ability to discharge. Journal of Comorbidity 2016;6(2):35–4

The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive) proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate cytokines, but also the loss of membrane receptors, adhesion molecules and T-cell cytokines that drive the aetiology of Buruli ulcer

Tax expenditures and progress to the Sustainable Development Goals

Action Aid International Professor Sonia Buist Global Child Health Research Fund Scottish Funding CounciThis study reports the impact of governments having additional revenue equivalent to tax expenditures on achieving the Sustainable Development Goals in 97 countries. The study draws data on revenue foregone from the Global Tax Expenditure Database. To analyze the potential of an increase in government revenue equivalent to the revenue foregone, the study uses the Government Revenue and Development Estimations modeling. The study finds that if governments had additional revenue equivalent to tax expenditures: an additional 17 million children would attend school (13.62% currently out of school), an additional 70 million people would use basic water (23% of those without access), 146 million would use basic sanitation (20% of those without access), 181,000 children would survive (13% of children who currently die), and 12,000 mothers would survive (16% of mothers who currently die). Critically, there would be improvements in governance indicators in all regions. Foregone revenue from tax expenditures could increase access to public services for millions, which is the most effective tool for reducing inequality and driving progress toward sustainable development. The massive opportunity costs reported here require all governments to report and justify their annual tax expenditure.Peer reviewe